Table 3. Summary of the HEIDI testing for pleiotropy versus LD between variants coassociated with IgG glycan levels, complex traits, and gene expression.
All traits have significant (PSMR ≤ 9.1 × 10−4) coassociation. In these loci where the associated variant was the same in IgG glycosylation, complex traits, and gene expression, we report only glycans pleiotropic with both expression and complex traits. The HEIDI test distinguishes between pleiotropy (shared causal variant, HEIDI P ≥ 0.05) or causal variants in LD (HEIDI P < 0.05). Glycan trait descriptions: G, galactose; F, fucose; N, bisecting GlcNAc; S, sialic acid; gene expression: CD4 and CD8, helper and cytotoxic T cells; CD19, B cells; PB, peripheral blood.
| Locus | IGP | Glycan description | Complex traits | SMR direction |
Gene expression |
SMR direction |
| Shared causal variant (pleiotropy) | ||||||
| IRF1-SLC22A4 | IGP2 and IGP42 |
G0 | CD | + | SLC22A4 (PB) | − |
| ORMDL3- GSDMB- IKZF3-ZPBP2 |
IGP2, IGP6, IGP42, and IGP46 |
G0 and G1 | Asthma, HDL, PBC, IBD, RA, and UC |
+ |
ORMDL3 (CD4, CD8, CD19, and PB) |
− |
|
GSDMB (CD19 and PB) |
− | |||||
| IKZF3 (PB) | + | |||||
| IGP58, IGP59, IGP60, and IGP61 |
% Fucosylation in total and in agalactosylated/ monogalactosylated/ digalactosylated glycans |
Asthma, PBC, HDL, RA, and UC |
− |
ORMDL3 (CD4, CD8, CD19, and PB) |
+ | |
|
GSDMB (CD19 and PB) |
+ | |||||
| IKZF3 (PB) | − | |||||
| CRHR1-SPPL2C- MAPT- ARHGAP27 |
IG14, IGP49, and IGP54 |
G1FN, G2FN, % fucosylation of G1 glycans |
PD | − | ||
| Distinct causal variants in LD | ||||||
| RUNX3 | IGP65, IGP69, IGP74, IGP75, and IGP76 |
Ratio of fucosylated digalactosylated structures |
Ankylosing spondylitis |
|||
| IRF1-SLC22A4 | IGP2 and IGP42 |
G0 | Height and IBD | |||